Vaccination
The generation of protective immunity against a pathogen in a manner that does not itself cause pathological disease
Epidemiological principle of vaccination
The goal for a vaccination program is to prevent disease in individuals and thereby reduce the disease burden of the herd to enhance the public health. When over 80% of a population’s individuals are immune, it begins to become mathematically difficult for pathogens to spread effectively.
Immunological principle of vaccination
To stimulate a primary adaptive immune response in the absence of clinical disease to generate immunological memory and thereby prevent or truncate future occurrence of clinical disease.
once you reach 60-65 you stop mounting immune responses effectively
% of population immunized for herd immunity
80%
Features of an effective vaccine
- safe
- protective
- Gives sustained protection
- Induces neutralizing antibodies: doesn’t have to but some pathogens infect cells that cannot be replaced
- Induces protective T cells: rare, effective for intracellular pathogens
- Low-cost, stability, ease of administration, few side effects
Adjuvantation
Provision of the danger signals necessary to trigger innate inflammation through pattern recognition receptors via PAMPs and DAMPs
3 approved adjuvants
- Alum
- MPL
- mRNA
- Needle from vaccination is a form of adjuvantation
Alum
- Most commonly used adjuvant in vaccines licensed in the US. Alum is a mixture of several aluminum salts (hydroxide, sulfate, phosphate) in varying proportions.
- provides a scaffold for the formation of the inflammasome
MPL
Monophosphoryl lipid A. A cell wall component of Salmonella enterica that binds and signals through TLR-4.
What PRRs does mRNA signal through
It signals through a variety of intracellular PRR, most prominently MDA5 but also RIG-I, TLR-7, and TLR-8.
Pathway from antigen uptake to T cell activation
- Antigen uptake by Langerhans cells
- Langerhans cells leave the skin and enter the lymphatic system
- CCR7 directs migration into the lymphoid tissues and augments expression of costimulatory and MHC molecules
- Mature DCs enter the lymph node from infected tissues and can transfer some antigens to resident DCs
- B7 positive DCs stimulate native T cells
What is boosting and why do it
- The antigenic stimulation of memory cells
Why? - Enhance longevity of the memory response
- Better protection
- Less frequent re-vaccination
When do you want to give a booster
- once memory cells have been developed
- No use boosting if you haven’t developed memory cells – timing needs to be worked out empirically – one of the main reasons that developmental timeline of vaccines is 20 yrs
Why does Edward Jenner deserve the credit for creating the smallpox vaccine
- Large Cohort
- Demonstrated ability of protective immunity to be passed between people and not just from bovine hosts
- Demonstrated bone fide smallpox immunity by subsequent variolation after vaccination: experimentation and documentation vs. anecdotalism
Koch’s Postulates?
Antigen
A substance (usually a macromolecule) that induces an immune response.
Adjuvant
- Immunologic danger
- In the context of immunology, is a substance added to a vaccine that is not an antigen, but which enhances the immunogenicity of the vaccine to the antigen.
Antigen Depot
- A substance that aggregates antigen into large complexes and improves their uptake by APC, recognition by B cell receptors and releases antigen slowly over an extended period of time.
- An effective antigen depot can avoid boosting
Haptens and Carriers
- A hapten is a small molecule that can elicit an immune response only when attached to a large carrier such as a protein. Large molecules, infectious agents, or insoluble foreign matter elicit immune responses.
- Hapten can technically be recognized by B cell, but since it can’t be presented you can’t get T cell help
Name the 6 different types of vaccines
- Live-Attenuated
- Inactivated (killed)
- Subunit
- Carrier
- Recombinant
- mRNA
Live-Attenuated vaccines
- Live virus or bacteria that infect the vaccine recipient but do not cause disease
- causes an infection that is subclinical
- Examples: Measles, Mumps, Rubella, some influenza vaccines (Flumist), Polio (Sabin vaccine)
Inactivated (killed) vaccines
- Wild type infectious pathogens rendered inactive either by chemical (formalin fixation) or thermal treatment.
- Examples: Hepatitis A, seasonal influenza vaccine, Cholera, Polio (Salk vaccine).
Subunit vaccines
- Purified or recombinant component protein sub-units of a pathogen, such as viral surface antigens or attenuated bacterial toxins (toxoids).
- Examples: Hepatitis B, HPV, Tetanus, Diptheria.
